Abstract: The non-receptor Src homology 2 domain-containing protein tyrosine phosphatase （SHP2） was encoded by PTPN11, converging multiple signaling pathways in tumor cells. SHP2 was involved in the pathogenesis of many different malignancies, including non-small cell lung cancer （NSCLC）. SHP2 regulated cell proliferation, apoptosis, invasion, and metastasis in lung cancer. In several models of therapeutic resistance, the combination of SHP2 inhibitors with other therapies can regress resistant tumors and remodel the tumor microenvironment. This paper reviews the biological functions of SHP2 in NSCLC, and summarizes the development of SHP2 inhibitors and their applications in NSCLC, showing the great potential of SHP2 as a drug target for NSCLC.